{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:09:39Z","timestamp":1789816179542,"version":"4.0.1"},"reference-count":125,"publisher":"SAGE Publications","issue":"s1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,10,18]]},"abstract":"<jats:p>Alzheimer\u2019s disease (AD) and Down syndrome (DS) share a common therapeutic target, the dual-specificity, tyrosine phosphorylation activated kinase 1A (DYRK1A). Abnormally active DYRK1A is responsible for cognitive disorders (memory, learning, spatial localization) observed in both conditions. In DS, DYRK1A is overexpressed due to the presence of the DYRK1A gene on chromosome 21. In AD, calcium-activated calpains cleave full-length DYRK1A (FL-DYRK1A) into a more stable and more active, low molecular weight, kinase (LMW-DYRK1A). Genetic and pharmacological experiments carried out with animal models of AD and DS strongly support the idea that pharmacological inhibitors of DYRK1A might be able to correct memory\/learning disorders in people with AD and DS. Starting from a marine sponge natural product, Leucettamine B, Perha Pharmaceuticals has optimized, through classical medicinal chemistry, and extensively characterized a small molecule drug candidate, Leucettinib-21. Regulatory preclinical safety studies in rats and minipigs have been completed and formulation of Leucettinib-21 has been optimized as immediate-release tablets. Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented.<\/jats:p>","DOI":"10.3233\/jad-240078","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T10:52:38Z","timestamp":1729248758000},"page":"S95-S113","source":"Crossref","is-referenced-by-count":32,"title":["Leucettinib-21, a DYRK1A Kinase Inhibitor as Clinical Drug Candidate for Alzheimer\u2019s Disease and Down Syndrome"],"prefix":"10.1177","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-4916","authenticated-orcid":false,"given":"Laurent","family":"Meijer","sequence":"first","affiliation":[{"name":"Perha Pharmaceuticals, H\u00f4tel de Recherche, Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Chr\u00e9tien","sequence":"additional","affiliation":[{"name":"Perha Pharmaceuticals, H\u00f4tel de Recherche, Roscoff, Bretagne, 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